Amantadine CAS 768-94-5
Introduction：Basic information about Amantadine CAS 768-94-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Amantadine Basic informationInhibitor
| Product Name: | Amantadine |
| Synonyms: | 1-ADAMANTYLAMINE;1-ADAMANTANAMINE;1-ADAMANTAMINE;1-AMINOADAMANTANE;1-Adamantanamin;1-Amantadine;1-Aminoadamatane;1-aminodiamantane |
| CAS: | 768-94-5 |
| MF: | C10H17N |
| MW: | 151.25 |
| EINECS: | 212-201-2 |
| Product Categories: | A-AM;Amines;Bioactive Small Molecules;Building Blocks;C10;Cell Biology;Chemical Synthesis;Nitrogen Compounds;Organic Building Blocks;Adamantane derivatives;neurochemistry |
| Mol File: | 768-94-5.mol |
Amantadine Chemical Properties
| Melting point | 206-208 °C(lit.) |
| Boiling point | 263.29°C (rough estimate) |
| density | 0.9510 (rough estimate) |
| refractive index | 1.5220 (estimate) |
| storage temp. | Keep in dark place,Inert atmosphere,Room temperature |
| solubility | 1 M HCl: soluble5%, clear to hazy, colorless to faint yellow or tan |
| form | Powder |
| pka | 10.1(at 25℃) |
| color | White to cream |
| Water Solubility | Soluble in organic solvents. Insoluble in water. |
| Merck | 14,374 |
| BRN | 2204333 |
| Major Application | food and beverages personal care pharmaceutical |
| InChI | 1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2/t7-,8+,9-,10- |
| InChIKey | DKNWSYNQZKUICI-UHFFFAOYSA-N |
| SMILES | NC12C[C@H]3C[C@H](C[C@H](C3)C1)C2 |
| CAS DataBase Reference | 768-94-5(CAS DataBase Reference) |
| NIST Chemistry Reference | Tricyclo[3.3.1.13,7]decane-1-amine(768-94-5) |
| EPA Substance Registry System | Tricyclo[3.3.1.13,7]decan-1-amine (768-94-5) |
Safety Information
| Hazard Codes | Xn,Xi |
| Risk Statements | 22-36/37/38 |
| Safety Statements | 26-36 |
| WGK Germany | 3 |
| RTECS | YD1925000 |
| F | 10-34 |
| TSCA | TSCA listed |
| HS Code | 29213000 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral Eye Irrit. 2 Skin Irrit. 2 STOT SE 3 |
| Hazardous Substances Data | 768-94-5(Hazardous Substances Data) |
| Toxicity | LD50 oral in rat: 900mg/kg |
| Inhibitor | The anti-influenza A compound amantadine acts by blocking the M2 ion channel which is required for uptake of protons into the interior of the virus to permit acid-promoted viral uncoating (decapsidation). |
| Description | Amantadine is an agent that raises the concentration of dopamine in the synaptic cleft byreleasing it from neurons and suppressing the process of reuptake. |
| Chemical Properties | White to cream powder |
| Uses | Building block for an L-piperidinamide catalyst used in an enantioselective Strecker reaction of phosphinoyl imines.1 |
| Uses | Amantadine is a primary amine derivative of adamantane. It has an effect on mycoviruses,which are RNA-containing viruses. It has a very narrow spectrum of action and is used only fortreating and preventing influenza A. It is also used for treating Parkinsonism. The exact mechanism of antiviral action of amantadine is not completely understood. It is believed that it is anion channel blocker. It has also been suggested that amantadine inhibits absorption of viral particles into the host cell, which is expressed in the breakdown of diffusion of the virus into thecell, or inhibition of the “stripping process” of the virus. The main use is for the prevention oftype A2 influenza. Synonyms of this drug are simmetrel, viregit, mantadan, and others. |
| Uses | Amantadine is an antiviral drug. The properties in amantadine, which relieve symptoms of Parkinsonism were discovered by accident. Treatment of Parkinsonism with a combination of levodopa,anticholinergic drugs, and amantadine gives better results than using any of these drugsindividually. |
| Definition | ChEBI: A member of the class of adamantanes that is used as an antiviral and antiparkinson drug. |
| Brand name | Symadine (Solvay Pharmaceuticals); Symmetrel(Endo). |
| Biological Functions | Amantadine was originally introduced as an antiviralcompound, but it is modestly effectivein treating symptoms of parkinsonism. It is useful in theearly stages of parkinsonism or as an adjunct to levodopatherapy. Its mechanism of action in parkinsonismis not clear, but amantadine may affect dopaminerelease and reuptake. Additional sites of action mayinclude antagonism at muscarinic and N-methyl-Daspartate(NMDA) receptors. Adverse effects includenausea, dizziness, insomnia, confusion, hallucinations,ankle edema, and livedo reticularis. Amantadine andthe anticholinergics may exert additive effects on mentalfunctioning |
| Synthesis Reference(s) | Journal of the American Chemical Society, 91, p. 6457, 1969 DOI: 10.1021/ja01051a047 Synthesis, p. 457, 1976 |
| Antimicrobial activity | It inhibits influenza A virus replication at concentrations of0.2–0.6 mg/L, but has little or no activity against influenzaB or C. |
| Acquired resistance | Resistance is the consequence of mutations in amino acidpositions 27, 30 and 31 in the M2 transmembrane sequence.Cross-resistance between amantadine and rimantadine is universal.Influenza H3N2 strains worldwide are now resistant,but seasonal H1N1 strains remain susceptible. Postexposurefamily prophylaxis results in the prompt emergence of drugresistance after onset of treatment. |
| General Description | Amantadine has been used for years as a treatment for Parkinson disease. The adamantanamines have twomechanisms in common:they inhibit an early step in viralreplication, most likely viral uncoating,and in somestrains, they affect a later step that probably involves viral assembly,possibly by interfering with hemagglutinin processing.The main biochemical locus of action is the influenzatype A virus M2 protein, which is an integral membrane proteinthat functions as an ion channel. The M2 channel is a protontransport system. By interfering with the function of theM2 protein, the adamantanamines inhibit acid-mediated dissociationof the ribonucleoprotein complex early in replication.They also interfere with transmembrane proton pumping,maintaining a high intracellular proton concentrationrelative to the extracellular concentration and enhancingacidic pH-induced conformational changes in the hemagglutininduring its intracellular transport at a later stage. The conformationalchanges in hemagglutinin prevent transfer of thenascent virus particles to the cell membrane for exocytosis. |
| Flammability and Explosibility | Flammable |
| Pharmaceutical Applications | A symmetrical synthetic C-10 tricyclic amine with an unusualcage-like structure, supplied as the hydrochloride for oraladministration. |
| Mechanism of action | Amantadine hydrochloride (1-adamantanamine hydrochloride) is a symmetric, tricyclic, primary amine thatinhibits penetration of RNA viral particles into the host cell. It also inhibits the early stages of viralreplication by blocking the uncoating of the viral genome and the transfer of nucleic acid into the hostcell. |
| Pharmacokinetics | Oral absorption: >90% Cmax 200 mg oral per day: 0.4–0.9 mg/L after c. 4–6 h Plasma half-life: 9.7–14.5 h Volume of distribution: 10.4 L/kg Plasma protein binding: 65% Absorption and distribution Absorption after oral administration is almost complete. Levels in secretions approach plasma concentrations. Metabolism and excretion About 56% of a single oral dose is excreted unchanged within 24 h by the kidney. Altogether 90% of an oral dose is excreted in the urine with a mean elimination half-life of 11.8 h in subjects with normal renal function. In elderly men, the half-life is 28.9 h and in patients with renal insufficiency half-lives of 18.5 h to 33.8 days have been observed. The renal clearance is around 398 mL/min (range 112–772 mL/min), indicating active secretion as well as glomerular filtration. Less than 5% of a dose is removed during hemodialysis and average half-lives of 8.3 and 13 days have been reported in patients on chronic hemodialysis. Extreme care must be taken to ensure that drug does not accumulate to toxic levels. |
| Clinical Use | Prevention and treatment of influenza A H1N1 infections |
| Clinical Use | Amantadine is used for the treatmentof diseases caused by influenza A strains. |
| Side effects | Embryotoxicity and teratogenicity have been observed in ratsreceiving 50 mg/kg per day, about 15 times the usual humandose. Neurological side effects include drowsiness, insomnia,light-headedness, difficulty in concentration, nervousness, dizzinessand headache in up to 20% of individuals. Other sideeffects include anorexia, nausea, vomiting, dry mouth, constipationand urinary retention. All develop during the first3–4 days of therapy and are reversible by discontinuing thedrug. An exception to rapid onset of adverse reactions is livedoreticularis. Convulsions, hallucinations and confusion are doserelated, usually occurring at levels in excess of 1.5 mg/L; convulsionsmay occur at a lower threshold in patients with a historyof epilepsy and the drug is best avoided in such patients. |
| Safety Profile | Poison by intraperitoneal route.Moderately toxic by ingestion. Mutation data reported.When heated to decomposition it emits toxic fumes ofNOx. Used as an antiviral agent. |
| Synthesis | Amantadine, 1-adamantanamine (10.1.12), is synthesized from adamantane. It is directly brominated to 1-bromadamantane (10.1.10), which in Ritter reactionconditions when heated with a mixture of acetonitrile and concentrated sulfuric acid transforms into 1-acetylaminoadamantane (10.1.11). Hydrolysis of this product using alkalileads to the formation of amantadine (10.1.12) [16,17]. |
| Purification Methods | Dissolve the amine in Et2O, dry it over KOH, evaporate and sublime it in vacuo. [Stetter et al. Chem Ber 93 226 1960.] |
Amantadine Preparation Products And Raw materials
| Raw materials | Bromine-->Adamantane-->Distillator-->Industrial glass lining reaction vessel |
| Preparation Products | 1-Adamantanamine hydrochloride-->1-ADAMANTYL ISOTHIOCYANATE-->N-ADAMANTAN-1-YL-PHTHALAMIC ACID-->CHEMBRDG-BB 5636113-->1-(1-ADAMANTYL)PYRROLIDIN-2-ONE |
